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Heppt, M.V.* ; Wang, J.X.* ; Hristova, D.M.* ; Wei, Z.* ; Li, L.* ; Evans, B.* ; Beqiri, M.* ; Zaman, S.* ; Zhang, J.* ; Irmler, M. ; Berking, C.* ; Besch, R.* ; Beckers, J. ; Rauscher, F.J.* ; Sturm, R.A.* ; Fisher, D.E.* ; Herlyn, M.* ; Fukunaga-Kalabis, M.*

MSX1-induced neural crest-like reprogramming promotes melanoma progression.

J. Invest. Dermatol. 138, 141-149 (2018)
Verlagsversion Postprint DOI
Open Access Green
Melanoma cells share many biological properties with neural crest stem cells. Here we show that the homeodomain transcription factor Msh homeobox 1 (MSX1), which is significantly correlated with melanoma disease progression, reprograms melanocytes and melanoma cells towards a neural crest precursor-like state. MSX1-reprogrammed normal human melanocytes express the neural crest marker p75 and become multipotent. MSX1 induces a phenotypic switch in melanoma, which is characterized by an oncogenic transition from an E-cadherin-high non-migratory state towards a ZEB1-high invasive state. ZEB1 up-regulation is responsible for the MSX1-induced migratory phenotype in melanoma cells. Depletion of MSX1 significantly inhibits melanoma metastasis in vivo. These results demonstrate that neural crest-like reprogramming achieved by a single factor is a critical process for melanoma progression.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Mesenchymal Stem-cells; Transcription Factor; Liver-diseases; Expression; Cancer; Microphthalmia; Melanocytes; Phenotype; Gene; Msx1
ISSN (print) / ISBN 0022-202X
e-ISSN 1523-1747
Quellenangaben Band: 138, Heft: 1, Seiten: 141-149 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort New York, NY
Begutachtungsstatus Peer reviewed